The compounds of this invention exhibit V.sub.1 and/or V.sub.2 vasopressin antagonist activity. Vasopressin is known to contribute to the antidiuretic mechanism of actions within the kidney. The action of these compounds antagonizes that of the natural anti-diuretic hormone (ADH) so as to cause the body to excrete water.
M. Manning et al., Nature, 308 652 (1984) and U.S. Pat. No. 4,469,679 have disclosed that the terminal glycine unit at the 9-position of certain vasopressin-like antagonists can be removed or replaced by L or D-Ala, Ser or Arg without necessarily affecting the binding at vasopressin receptors.
U.S. Pat. Nos. 4,481,194 and 4,481,193 have disclosed that removing proline at position 7 or both proline and glycine at positions 7 and 9 from the structures of vasopressin antagonist compounds will produce compounds which retain substantial, but somewhat reduced, antagonist activity.
The compounds of this invention have structures which are distinguished over the prior art in that three basic amino acid units, such as arginine, lysine or ornithine are attached directly to the disulfide vasopressin-like ring. The compounds of this invention are potent vasopressin antagonists.